No Priors: Artificial Intelligence | Technology | Startups

Technology has always been the fundamental driver of improvement for human quality of life. And with the recent rollout of advanced frontier models, like OpenAI’s GPT-6, humanity can now massively accelerate scientific discovery for its benefit. Sarah Guo and Elad Gil are joined by OpenAI President and co-founder Greg Brockman to discuss the company’s rapid progress across frontier models, cybersecurity, and scientific discovery. Greg shares how nearly 400 century-old math problems have been solved using its AI agents, and how the technology has the potential to transform other fields like biology in the realm of drug discovery. He also talks about how proactive, always-on AI agents like Dots impact modern productivity, why he believes the best UI is no UI at all, how cybersecurity is in a critical window of time to use peak intelligence to find and fix vulnerabilities in systems, and why OpenAI remains committed to keeping humans in the driver’s seat even as models surpass us in capability.

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Chapters:

00:42 – Trailer

00:59 – Greg Brockman Introduction

01:11 – AI and Advancements in Mathematics

05:55 – AI Communication and Oversight

07:45 – AI for Overcoming Biology Data Bottlenecks

11:28 – Revolutionizing Drug Discovery

14:18 – Changing Regulations to Accelerate Progress

16:51 – Dots the Proactive Agent

19:19 – Unifying Work and Consumer Agents

22:02 – How UI Will Evolve

26:08 – Cybersecurity in the AI Age

32:55 – Shift in Security Investment

35:49 – OpenAI’s Human-Centric Ethos

38:28 – Conclusion

Is the future of frontier AI open or closed? ReflectionAI co-founder and CEO Misha Laskin joins Sarah Guo and Elad Gil to discuss the launch of Beam, the company’s 500 billion parameter open-weight reasoning model. Misha breaks down the pre-training and reinforcement learning required to produce Beam’s reasoning efficiency, the shift in enterprise compute from renting to owning intelligence, and how he believes that open models will capture the majority of global token demand. He also talks about the open model ecosystem in China and why competition with China’s models is a good thing, safety considerations around open models, and how frontier-level open models may accelerate the pace of scientific discovery.  

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Chapters:

00:42 – Misha Laskin Introduction

00:59 – Latest with ReflectionAI

02:07 – Challenges Building an Open Model

03:56 – ReflectionAI’s Agentic Shift

07:37 – Resources for Model Training

10:09 – Scaling Efficiency

12:18 – Training Beam

16:51 – Where Model Value Comes From

19:55 – Beam’s Reasoning Efficiency

22:35 – Monetizing Open Weight Models

25:03 – Future of Open Versus Closed Tokens

31:29 – Competition with Open Models

34:38 – Chinese Open Source Model Ecosystem

38:40 – Will Chinese Models Remain Open

44:44 – Safety and Open Models

53:02 – Debating Access to Powerful Tools

57:16 – AI and Scientific Progress

01:00:36 – Data Centers and Jobs

01:02:07 – Beam and Scientific Research

01:05:37 – Research Head Count to Compute Ratio

01:10:29 – Conclusion

Founder and CEO of full-stack AI chip company Fractile, Walter Goodwin, joins Sarah Guo to discuss the bets he’s made on the future of the chip market as other major players like Broadcom, NVIDIA, and AMD try to accelerate their workloads. They discuss the difference in Fractile’s newer approach on model architecture with a full-stack team in the current chip landscape and the technical bets they’re making in that direction. Walter also talks about compressing the gap between the chip design cycle and its payoff period, and making a generational leap in AI inference to realize the bet in volume against the value to be captured. 

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Chapters:

00:46 – Walter Goodwin and Fractile Introduction 

02:29 – The Chip Landscape Now

04:56 – Common Handoffs From Architecture-Focused Players

07:18 – Full Stack Approach and Team Setup

09:49 – Fractile’s Most Important Technical Bets 

15:32 – Workload Predictions and Compressing the Chip Design Cycle

23:03 – Architect Intent to Output Bottlenecks and Accelerating Trials

28:16 – Workload Bets on Model Architectural Shifts

31:20 – The Future of AI Chip Players and Market Structure  

35:14 – Conclusion

Can AI transform legacy incumbents rather than replacing them? Sequence Holdings co-founder and CEO Michael Lee joins Sarah Guo to discuss how holding company structures and engineering integrations are reshaping market leaders from the inside out. Michael details Sequence’s $7.7 billion take-private transaction of Baldwin alongside Dell Family Office (DFO), and shares his thesis on why traditional consulting models and software sales fall short for real enterprise AI transformations. They also talk about why permanent holding company structures are good for long-term compounding, real-world results from applying frontier engineering to BankSouth, and Michael’s lessons from his time in public investing, private equity, and operating at the intersection of market incumbents and AI.

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Chapters:

00:34 – Michael Lee Introduction

01:03 – Sequence Holdings and Baldwin

01:54 – Idea for Sequence

04:36 – Incumbents in the AI Era

06:32 – Why a Holding Company

11:21 – Recruiting Top Engineers

13:08 – Investing in BankSouth

17:46 – Why an Insurance Brokerage

20:17 – Atlas Platform Explained

23:53 – Traditional Private Equity Limitations

27:23 – What Sequence Looks For in Management Teams

31:04 – Accomplishments at BankSouth

34:45 – Founder Lessons

36:08 – Story of Dell Partnership

37:10 – Career and Investment Approach

40:00 – Value of Exceptional People

42:23 – Conclusion

As generative AI hits hardware and latency bottlenecks, Stanford professor, diffusion pioneer, and Inception co-founder and CEO Stefano Ermon is betting on a radical new architecture. Stefano joins Sarah Guo to talk about Inception, and how his team is applying diffusion architecture beyond images and video into discrete text and code generation. Stefano explains the limitations of autoregressive LLMs, as well as why parallel token generation in diffusion models offers superior inference scaling and hardware utilization on standard GPUs. He also shares details about Inception’s Mercury models, real-world voice agent applications, the software stack required to serve diffusion-based models at scale, academia’s role at the frontier of AI innovations, and why the next era of AI competition will be defined by efficiency. 

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Chapters:

00:00 – Stefano Ermon Introduction

00:35 – Research Background

02:54 – Starting Inception

05:59 – Why Diffusion Beats Autoregressive

11:10 – Discrete vs. Continuous Modalities

13:19 – Inception Today

16:45 – Where Speed Wins

17:31 – Inception Customer Base

18:49 – Interaction with Hardware Landscape

19:34 – Inception and the Broader Industry

21:41 – Data Compression and Structure

24:45 – Controllability of Diffusion Modeles

27:25 – Emergent Capabilities at Scale

29:02 – Future Workload Split Between Diffusion vs. Traditional

30:03 – Adoption Challenges

31:44 – Hiring and Team Organization

32:50 – Recursive Self Improvement

34:02 – Resource Allocation

35:10 – Impact of Academia

38:13 – Conclusion

From the tokenization of real-world assets to funding research on anti-aging therapeutics, Coinbase co-founder and CEO Brian Armstrong is focused on solving meta-problems for the benefit of society. Brian joins Elad Gil this episode to discuss the intersections of artificial intelligence, crypto rails, and biotechnology. He details Coinbase’s vision for agentic finance, as well as how Coinbase is becoming the ‘Everything Exchange’, which includes tokenized real-world stocks, stablecoin payment adoption, and prediction markets. Brian also introduces his new venture, New Limit, a company founded to tackle longevity through epigenetic reprogramming, and outlines initial therapeutic programs and the roadmap toward clinical trials.  

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Chapters:

00:00 – Cold Open Trailer

00:45 – Brian Armstrong Introduction

01:13 – Coinbase and the Everything Exchange

05:52 – Agentic Commerce

10:00 – AI and Crypto

10:49 – AI Inside Coinbase

15:39 – Productivity and Company Size

17:26 – The Everything Exchange and Tokenization

20:53 – Prediction Markets

23:15 – Introducing New Limit

34:17 – Looking Forward Five Years

40:24 – Special Economic Zones

44:26 – Conclusion

From data center orchestrators to AGI and robotics, CPUs remain the heart of modern computing. Arm CEO Rene Haas joins Elad Gil and Sarah Guo to explore how Arm is positioned at the epicenter of AI-driven demands for compute. Rene explains Arm’s position in the chip supply chain, and how Arm transitioned from an IP licensing model to producing physical chips like the Arm AGI CPU for Meta. He also discusses bottlenecks in hardware supply chains, SoftBank’s ecosystem and capital strategy, why US semiconductor manufacturing independence is critical, the future of robotics, and why CPUs remain crucial for executing AI workloads.

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Chapters:

00:00 – Cold Open Trailer

00:49 – Rene Haas Introduction

01:14 – Arm and Chip Supply Chain

02:37 – Shift from IP to Manufacturing CPUs

04:23 – CPU IP and Customers

06:55 – AI Adoption at Arm

10:15 – Changes in Chip Time to Market

13:27 – Data Center Buildout Bottleneck

15:13 – Softbank Leverage and Capital Strategy

17:43 – Softbank Portfolio Overview

20:13 – Robotics Opportunities for Arm

24:49 – US Manufacturing Protectionism

28:59 – Data Center Backlash

32:30 – Arm Outlook

33:31 – CPU Opportunity

37:06 – Conclusion

Google’s purchase of Spirit Airlines’ data out of bankruptcy signaled a shift in how the tech world values real-world datasets. Although compute and models get much of the attention, in this landscape, it’s data that is a company’s protective moat. Eon CEO / Co-Founder Ofir Ehrlich and President / Co-Founder Gonen Stein join Elad Gil to talk about how Eon is redefining cloud backup into a secure data foundation designed to power and protect enterprise AI. Ofir and Gonen discuss why historical enterprise data is in demand by AI labs, and how Eon facilitates access to scattered and locked data across business units through providing the mapping, classification, and access controls needed to connect it into AI workflows. They also explore how traditional ransomware defenses must now protect against rogue AI agents with legitimate system permissions, concerns around the influx of autonomous agents and non-human identities, and the implications for the breakneck speed of AI adoption compared to the slowness of the cloud era. 

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Chapters:

00:00 – Cold Open Trailer

00:59 – Ofir Ehrlich and Gonen Stein Introduction

01:27 – What Eon Does

02:41 – Data as Moat

06:43 – Training Agents with Good Data

09:39 – Data is the New Oil 

15:00 – Autonomous Security Threats

18:15 – How Agents Change the Enterprise Stack

22:11 – Re-imagining Data Infrastructure

27:52 – Cloud vs. AI Era Shift

30:26 – How AI is Changing Companies

34:31 – Conclusion

Max Hodak, co-founder and CEO of Science Corporation, joins Sarah Guo to discuss the future of vision, brain-computer interfaces, and the human experience. Max explains how Science’s PRIMA retinal implant could restore functional vision for people who have lost their sight, and why treating the brain as a computational system could unlock new approaches to medicine.

They explore the broader potential of neural devices, from restoring lost capabilities to expanding human potential, as well as deeper questions around identity, consciousness, and whether the human experience can persist as our biological hardware changes.

Max also shares Science’s long-term vision for reducing the fragility of the human condition by repairing, replacing, and ultimately upgrading parts of ourselves. Finally, he discusses the surprising parallels between AI models and biological brains, and why AI may offer a powerful new lens for understanding intelligence.

Chapters:

00:00 – Cold Open Trailer

01:40 – Max Hodak Introduction

02:00 – Science Corporation Overview and Origin

02:53 – A Revolutionary Solve for Blindness 

06:32 – Scope of Timeline and Engineer Cost

09:10 – Clinic Trial Process

09:45 - The Response from Clinicians

12:21 – Broader Biotech Landscape

14:59 – Brain’s Relationship to Senses

17:35 – The Study of Consciousness 

19:50 – Investments in Brain Computer Interface

22:10 – Fertile Ways to Study Neuroscience

24:46 – Biotech Expansion for Science Corporation

27:50 – What Success Looks Like in Neuroscience and Tech

29:06 - Goals Within Human Preservation vs. Adaptation 

30:25 – Conclusion

In a world of infinite gaming and entertainment possibilities, how does a centuries-old game stay so popular? Chess.com co-founder and CEO Erik Allebest joins Sarah Guo to explain how the evolution of technology has kept people coming back to chess, even when machines can beat us at the game. Erik talks about how the desire to build a MySpace-like community for chess led to the purchase of a domain name from a bankruptcy sale back in 2005, and scaled into a community with 10 million daily active users and 250 million total registered members. He also discusses the growth of the cultural relevance of chess, how investments from private equity firms General Atlantic and CVC helped grow and strengthen their platform, and how Chess.com is leveraging AI both within the business itself and to make a better product for its community.

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Chapters:

00:00 – Cold Open Trailer

01:05 – Erik Allebest Introduction

01:48 – Chess.com Today

02:57 – Buying and Scaling Chess.com 

06:29 – Competition and Growth

11:52 – Chess and Cultural Relevance

14:32 – Private Equity Investment

19:31 – Playing Games Amid Evolving Tech

25:09 – Tech, Skill Distribution, and Expertise

28:40 – Chess and Cheating

31:20 – What Makes Chess Special

33:17 – Chess.com Future Vision

34:54 – Founder Advice

36:48 – AGI/ASI Predictions

40:02 – AI Investments at Chess.com 

42:13 – How AI May Change Product at Chess.com

43:27 – Poker Rating Algorithms

46:07 – Conclusion